Mucosa-associated lymphoid tissue lymphoma: novel translocations including rearrangements of ODZ2, JMJD2C, and CNN3.
OBJECTIVE
The well-known translocations identified in MALT lymphomas include t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, and t(14;18)/IGH-MALT1. Molecular investigations have suggested that these three disparate translocations affect a common pathway, resulting in the constitutive activation of nuclear factor-kappaB. However, the vast majority of MALT lymphomas are negative for any of the above-mentioned translocations and the underlying pathogenesis is unclear.


METHODS
Fresh tissue of 29 gastric and extragastric MALT lymphomas was studied for genetic aberrations by conventional karyotyping, long-distance inverse PCR (LDI-PCR), fluorescence in situ hybridization (FISH), reverse transcription-PCR (RT-PCR), and real-time quantitative RT-PCR (QRT-PCR).


RESULTS
Conventional cytogenetics, FISH, and RT-PCR identified aberrations in 26 of 29 MALT lymphoma. Balanced translocations were found in 21 cases. IGH was rearranged in the majority of cases with balanced translocations (n = 17/21); 3 cases had t(11;18)/API2-MALT1 and 1 case had novel t(6;7)(q25;q11), respectively. IGH partner genes involved MALT1, FOXP1, BCL6, and four new chromosomal regions on chromosome arms 1p, 1q, 5q, and 9p. LDI-PCR identified three novel partner genes on 1p (CNN3), 5q (ODZ2), and 9p (JMJD2C). FISH assays were established and confirmed LDI-PCR results. QRT-PCR showed deregulation of the novel genes in the translocation-positive cases.


CONCLUSIONS
Our study expands the knowledge on the genetic heterogeneity of MALT lymphomas.
Vinatzer
Ursula
U
Department of Pathology and Internal Medicine 1, Medical University of Vienna, Vienna, Austria.
Gollinger
Michaela
M
Müllauer
Leonhard
L
Raderer
Markus
M
Chott
Andreas
A
Streubel
Berthold
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D056484:Jumonji Domain-Containing Histone Demethylases; D007621:Karyotyping; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*; D000096985:Calponins
D002135:Calcium-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D056484:Jumonji Domain-Containing Histone Demethylases; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; D019063:Tenascin; D014157:Transcription Factors; D000096985:Calponins; C415943:API2-MALT1 fusion protein, human; C413655:KDM4C protein, human; C120530:teneurin-1